活巨噬细胞递送的四足动物 PdH 纳米酶通过 ROS 清除、氢抗炎和自噬激活进行靶向动脉粥样硬化管理,ACS Nano

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活巨噬细胞递送的四足动物 PdH 纳米酶通过 ROS 清除、氢抗炎和自噬激活进行靶向动脉粥样硬化管理
ACS Nano ( IF 15.8 ) Pub Date : 2022-10-11 , DOI: 10.1021/acsnano.2c03422
Ruizhi Hu ₁ , Chen Dai ₁ , Caihong Dong ₂ , Li Ding ₃ , Hui Huang ₄ , Yu Chen ₄ , Bo Zhang ₁

Affiliation

由动脉壁慢性炎症驱动的动脉粥样硬化是几种严重心血管疾病的基础。然而，目前可用的基于抗炎的动脉粥样硬化治疗策略存在治疗效果受损和不良治疗结果的问题。在此，设计和设计了一种独特的四足针状 PdH 纳米酶，通过组合活性氧 (ROS) 清除、氢抗炎和自噬激活来有效治疗动脉粥样硬化。在加载到巨噬细胞中并靶向递送至动脉斑块后，这些多功能纳米酶有效地降低了活性氧水平并显着抑制了炎症相关的病理过程，发挥独特的抗氧化和抗炎作用，以减轻动脉粥样硬化的发展。特别重要的是，PdH 纳米酶的特定尖峰形态进一步引发了巨噬细胞中强烈的自噬反应，协同维持细胞稳态并缓解动脉粥样硬化的发展。两个都体外和体内结果证实了抗氧化、抗炎和自噬激活之间的协同作用，表明具有内在多重治疗功能和拓扑诱导生物效应的纳米药物的组合工程对于实现高治疗性能是非常优选和有效的。动脉粥样硬化管理和治疗的理想治疗结果。

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Living Macrophage-Delivered Tetrapod PdH Nanoenzyme for Targeted Atherosclerosis Management by ROS Scavenging, Hydrogen Anti-inflammation, and Autophagy Activation

Atherosclerosis, driven by chronic inflammation in the artery walls, underlies several severe cardiovascular diseases. However, currently available anti-inflammatory-based strategies for atherosclerosis treatment suffer from compromised therapeutic efficacy and undesirable therapeutic outcome. Herein, a distinct tetrapod needle-like PdH nanozyme was designed and engineered for efficient atherosclerosis treatment by the combinatorial reactive oxygen species (ROS) scavenging, hydrogen anti-inflammation, and autophagy activation. After loading into macrophages and targeted delivery to arterial plaques, these multifunctional nanozymes efficiently decreased the ROS levels and significantly suppressed the inflammation-related pathological process, exerting the distinct antioxidation and anti-inflammatory performance for alleviating atherosclerosis development. Especially and importantly, the specific spiky morphology of the PdH nanoenzyme further triggered a strong autophagy response in macrophages, synergistically maintaining the cellular homeostasis and alleviating atherosclerosis development. Both in vitro and in vivo results confirmed the synergy among the antioxidation, anti-inflammatory, and autophagy activation, suggesting that the combinatorial engineering of nanomedicines with intrinsic multiple therapeutic functions and topology-induced biological effects is highly preferable and effective for achieving the high therapeutic performance and desirable therapeutic outcome on atherosclerosis management and therapy.

更新日期：2022-10-11

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